PurposeAngiotensin II type 1 receptor blockers (ARBs) have been investigated for their neuroprotective and intraocular pressure (IOP) lowering effects in treating glaucoma, but the reports have been inconsistent possibly because different compounds and models have been used. Here we selected three ARBs for head-to-head comparisons of their effects on IOP and transforming growth factor β (TGFβ) signaling, which is believed to play an important role in glaucoma pathogenesis.MethodsThree ARBs (losartan, irbesartan or telmisartan) or vehicle controls were administered via chow to C57BL/6J mice for up to 7 days. Drug concentrations in the eye, brain, and plasma were evaluated by liquid chromatography mass spectrometry. Cohorts of mice were randomly assigned to different treatments. IOP and blood pressure were measured before and after ARB treatment. Effects of ARBs on TGFβ signaling in the retina were evaluated by phosphorylated Smad2 (pSmad2) immunohistochemistry.ResultsPhysiologically relevant concentrations of losartan, irbesartan and telmisartan were detected in eye, brain and plasma after drug administration (n = 11 mice/treatment). Blood pressure was significantly reduced by all ARBs compared to vehicle-fed controls (all p-values < 0.001, n = 8–15 mice/treatment). Compared to vehicle control, IOP was significantly reduced by irbesartan (p = 0.030) and telmisartan (p = 0.019), but not by losartan (n = 14–17 mice/treatment). Constitutive pSmad2 fluorescence observed in retinal ganglion cells was significantly reduced by telmisartan (p = 0.034), but not by losartan or irbesartan (n = 3–4 mice/treatment).ConclusionsAdministration via chow is an effective delivery method for ARBs, as evidenced by lowered blood pressure. ARBs vary in their abilities to lower IOP or reduce TGFβ signaling. Considering the significant roles of IOP and TGFβ in glaucoma pathogenesis, specific ARBs with dual effects, such as telmisartan, may be more effective than other ARBs for treating glaucoma.

Plants and photosynthetic organisms have a remarkably inefficient enzyme named Rubisco that fixes atmospheric CO 2 into organic compounds. Understanding how Rubisco has evolved in response to past climate change is important for attempts to adjust plants to future conditions. In this study, we developed a computational workflow to assemble de novo both large and small subunits of Rubisco enzymes from transcriptomics data. Next, we predicted sequences for ancestral Rubiscos of the (nightshade) family Solanaceae and characterized their kinetics after coexpressing them in Escherichia coli . Predicted ancestors of C 3 Rubiscos were identified that have superior kinetics and excellent potential to help plants adapt to anthropogenic climate change. Our findings also advance understanding of the evolution of Rubisco’s catalytic traits.

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